» Articles » PMID: 7515147

ErbB3 is Involved in Activation of Phosphatidylinositol 3-kinase by Epidermal Growth Factor

Overview
Journal Mol Cell Biol
Specialty Cell Biology
Date 1994 Jun 1
PMID 7515147
Citations 211
Authors
Affiliations
Soon will be listed here.
Abstract

Conflicting results concerning the ability of the epidermal growth factor (EGF) receptor to associate with and/or activate phosphatidylinositol (PtdIns) 3-kinase have been published. Despite the ability of EGF to stimulate the production of PtdIns 3-kinase products and to cause the appearance of PtdIns 3-kinase activity in antiphosphotyrosine immunoprecipitates in several cell lines, we did not detect EGF-stimulated PtdIns 3-kinase activity in anti-EGF receptor immunoprecipitates. This result is consistent with the lack of a phosphorylated Tyr-X-X-Met motif, the p85 Src homology 2 (SH2) domain recognition sequence, in this receptor sequence. The EGF receptor homolog, ErbB2 protein, also lacks this motif. However, the ErbB3 protein has seven repeats of the Tyr-X-X-Met motif in the carboxy-terminal unique domain. Here we show that in A431 cells, which express both the EGF receptor and ErbB3, PtdIns 3-kinase coprecipitates with the ErbB3 protein (p180erbB3) in response to EGF. p180erbB3 is also shown to be tyrosine phosphorylated in response to EGF. In contrast, a different mechanism for the activation of PtdIns 3-kinase in response to EGF occurs in certain cells (PC12 and A549 cells). Thus, we show for the first time that ErbB3 can mediate EGF responses in cells expressing both ErbB3 and the EGF receptor.

Citing Articles

Bilateral regulation of EGFR activity and local PI(4,5)P dynamics in mammalian cells observed with superresolution microscopy.

Abe M, Yanagawa M, Hiroshima M, Kobayashi T, Sako Y Elife. 2024; 13.

PMID: 39513999 PMC: 11548882. DOI: 10.7554/eLife.101652.


Leucine-Rich Alpha-2-Glycoprotein 1 Promotes Metastatic Colorectal Cancer Growth Through Human Epidermal Growth Factor Receptor 3 Signaling.

Rathore M, Curry K, Huang W, Wright M, Martin D, Baek J Gastroenterology. 2024; 168(2):300-315.e3.

PMID: 39393543 PMC: 11769768. DOI: 10.1053/j.gastro.2024.10.004.


Large-scale control over collective cell migration using light-controlled epidermal growth factor receptors.

Suh K, Thornton R, Farahani P, Cohen D, Toettcher J bioRxiv. 2024; .

PMID: 38853934 PMC: 11160748. DOI: 10.1101/2024.05.30.596676.


Global signal peptide profiling reveals principles of selective Sec61 inhibition.

Wenzell N, Tuch B, McMinn D, Lyons M, Kirk C, Taunton J Nat Chem Biol. 2024; 20(9):1154-1163.

PMID: 38519575 DOI: 10.1038/s41589-024-01592-7.


Busting the Breast Cancer with AstraZeneca's Gefitinib.

Chemmalar S, Intan Shameha A, Abdullah C, Ab Razak N, Mohamad Yusof L, Ajat M Adv Pharmacol Pharm Sci. 2023; 2023:8127695.

PMID: 38090376 PMC: 10713255. DOI: 10.1155/2023/8127695.


References
1.
Pike L, Eakes A . Epidermal growth factor stimulates the production of phosphatidylinositol monophosphate and the breakdown of polyphosphoinositides in A431 cells. J Biol Chem. 1987; 262(4):1644-51. View

2.
Thompson D, Cochet C, Chambaz E, Gill G . Separation and characterization of a phosphatidylinositol kinase activity that co-purifies with the epidermal growth factor receptor. J Biol Chem. 1985; 260(15):8824-30. View

3.
Rosen O . After insulin binds. Science. 1987; 237(4821):1452-8. DOI: 10.1126/science.2442814. View

4.
Whitman M, KAPLAN D, Roberts T, Cantley L . Evidence for two distinct phosphatidylinositol kinases in fibroblasts. Implications for cellular regulation. Biochem J. 1987; 247(1):165-74. PMC: 1148384. DOI: 10.1042/bj2470165. View

5.
King C, Borrello I, Bellot F, Comoglio P, Schlessinger J . Egf binding to its receptor triggers a rapid tyrosine phosphorylation of the erbB-2 protein in the mammary tumor cell line SK-BR-3. EMBO J. 1988; 7(6):1647-51. PMC: 457148. DOI: 10.1002/j.1460-2075.1988.tb02991.x. View